This proposal embodies five clinical research projects involving patients who have primary bladder carcinoma. These projects are conducted in several institutions simultaneously. All the pathological and cytological material are reviewed in a central pathology laboratory. All the data are being correlated in one statistical center. In each participating hospital, surveillance of all patients admitted with bladder carcinoma is being conducted. Multiple mucosal biopsies are obtained from patients with frank tumor and/or positive cytology and, in these patients, evaluation of urinary cytological examination is also carried out. Intravesical topical therapy, both ablative and prophylactic, is being conducted, with N N'N" -Triethylenethiophosphoramide (Thiotepa) on superficial carcinoma. For patients failing to respond to Thiotepa, Triethyleneglycoldiglycidyl (Epodyl) and Mitomycin C will be used. In invasive bladder carcinoma a comparison of the effects on survival and the quality of survival is being made between definitive radiotherapy alone and pre-operative radiotherapy followed by cystectomy. Finally, in patients with metastatic bladder carcinoma a program of systemic chemotherapy will be commenced. The first drugs studied will be Adriamycin and Cytoxan, but other agents will subsequently be used.